Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma
Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma
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DOI：
10.1007/s12253-019-00694-1
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发表时间：
2020-04-01
影响因子：
2.8
通讯作者：
Huang, Jie
中科院分区：
文献类型：
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作者：
Liu, Chao;Xu, Dingwei;Huang, Jie
肝细胞癌（HCC）是最常见的原发性肝癌类型，发生于慢性肝病患者。目前的治疗方法包括手术、移植和化疗。我们的研究证明了 runt 相关转录因子 1 (RUNX1) 作为 HCC 发生和发展中的一种新分子，及其与血管内皮生长因子 A (VEGFA) 相互作用在 HCC 中的作用。我们展示了 RUNX1 在肝细胞增殖和迁移中的抑制作用。此外，阻遏蛋白RUNX1作为VEGFA启动子上的转录因子发挥作用，抑制VEGFA的表达。 HCC 细胞研究表明，过度表达 VEGFA 的存在掩盖了对 HCC 增殖和迁移的抑制。将RUNX1引入HCC小鼠模型显着限制了肿瘤的生长。总之，我们的研究表明 RUNX1 在 HCC 中起到抑制因子的作用，并且这种抑制功能取决于其对 VEGFA 的作用。
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and occurs in people with chronic liver diseases. Current treatment methods include surgery, transplant, and chemotherapy. Our study demonstrates runt-related transcription factor 1 (RUNX1) as a novel molecule in the initiation and development of HCC, and the role of its interaction with vascular endothelial growth factor A (VEGFA) in HCC. We showed the suppressive role of RUNX1 in the proliferation and migration of hepatocytes. In addition, the repressor RUNX1 functioned as a transcription factor on the promoter of VEGFA to inhibit the expression of VEGFA. Study in the HCC cells demonstrated that the suppression of HCC proliferation and migration was masked in the presence of overexpressed VEGFA. Introduction of RUNX1 into HCC mice model significantly limited the tumor growth. In summary, our study demonstrated that RUNX1 functions as a repressor in the HCC and this suppressive function was dependent on its effect on VEGFA.